The use of simulation in the design of two cardiovascular survival studies

Simulation has become practical as an everyday tool given the wide availability of high performance workstations. We argue that simulation can play an important role in determining the number of patients required in a survival study, particularly if the assumption of proportional hazards does not hold, or if the study design is complex. The argument is illustrated by two examples. The first considers the design of a post myocardial infarction survival trial in which the hazard ratio is not constant. The second provides sample size estimates for a multicentre heart failure study in which both the treatment effect and the control mortality rate vary across centres.